Novel Aza-resveratrol analogs: Synthesis, characterization and anticancer activity against breast cancer cell lines

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Abstract

Novel Aza-resveratrol analogs were synthesized, structurally characterized and evaluated for cytotoxic activity against MDA-MB-231 and T47D breast cancer cell lines, which exhibited superior inhibitory activity than parent resveratrol compound. The binding mechanism of these compounds with estrogen receptor-α was rationalized by molecular docking studies which indicated additional hydrogen binding interactions and tight binding in the protein cavity. Induction of Beclin-1 protein expression in breast cancer cell lines after treatment with newly synthesized resveratrol analogs indicated inhibition of growth of these cell lines through autophagy. The study highlighted the advantage of introducing the imino-linkage in resveratrol motif in enhancing the anticancer potential of resveratrol suggesting that these analogs can serve as better therapeutic agents against breast cancer and can provide starting point for building more potent analogs in future.

Graphical abstract

Novel Aza-resveratrol analogs were synthesized, structurally characterized and evaluated for cytotoxic activity against MDA-MB-231 and T47D breast cancer cell lines, which exhibited superior inhibitory activity than parent resveratrol compound. The binding characteristics of the compounds with estrogen receptor-α (ER-α) were rationalized by molecular docking studies which indicated that these new Aza-resveratrol analogs favor additional hydrogen binding interactions than resveratrol and hence achieve more stability and tight binding in the protein cavity.

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References and notes (53)

  • W.J. Irvin et al.

    Eur. J. Cancer

    (2008)
  • H. Adlercreutz

    Lancet Oncol.

    (2002)
  • J.C. Le Bail et al.

    Life Sci.

    (2000)
  • P. Saiko et al.

    Mutat. Res.

    (2008)
  • D. Vergara et al.

    Cancer Lett.

    (2011)
  • Y. Li et al.

    Appl. Biochem. Biotechnol.

    (2006)
  • M. Alkhalaf et al.

    Arch. Med. Res.

    (2008)
  • R.H. Wang et al.

    Mol. Cell

    (2008)
  • A. Schlachterman et al.

    Transl. Oncol.

    (2008)
  • S. Garvin et al.

    Cancer Lett.

    (2006)
  • M. Asensi et al.

    Free Radic. Biol. Med.

    (2002)
  • A. Ahmad et al.

    Cancer Lett.

    (2000)
  • X. Gao et al.

    J. Nutr.

    (2002)
  • B.W. Moran et al.

    Bioorg. Med. Chem.

    (2009)
  • T.T. Wang et al.

    Mol. Nutr. Food Res.

    (2010)
  • M. Murias et al.

    Bioorg. Med. Chem.

    (2004)
    Y.J. Cai et al.

    Anticancer Res.

    (2004)
  • Y.M. Issa et al.

    Spectrochim. Acta, A Mol. Biomol. Spectrosc.

    (2011)
  • S. Ramalingam et al.

    Spectrochim. Acta, A Mol. Biomol. Spectrosc.

    (2011)
  • A.H. Kshash

    J. Chem.

    (2011)
  • K.V. Sashidhara et al.

    Tetrahedron Lett.

    (2007)
  • K.M. Khan et al.

    Bioorg. Med. Chem.

    (2009)
  • O. Corduneanu et al.

    Electroanalysis

    (2006)
  • X.H. Liang et al.

    Nature

    (1999)
  • A. Jemal et al.

    CA Cancer J. Clin.

    (2011)
  • A.G. Glass et al.

    J. Natl Cancer Inst.

    (2007)
  • O. Gluz et al.

    Ann. Oncol.

    (1913)
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